Diabetes reduces bone marrow and circulating porcine endothelial progenitor cells, an effect ameliorated by atorvastatin and independent of cholesterol

Emile R. Mohler, Yuquan Shi, Jonni Moore, Andrew Bantly, Damir Hamamdzic, Mervin Yoder, Daniel J. Rader, Mary Putt, Lifeng Zhang, Michael Parmacek, Robert L. Wilensky

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Bone marrow derived endothelial progenitor cells (EPCs) are early precursors of mature endothelial cells which replenish aging and damaged endothelial cells. The authors studied a diabetic swine model to determine if induction of DM adversely affects either bone marrow or circulating EPCs and whether a HMG-CoA reductase inhibitor (statin) improves development and recruitment of EPCs in the absence of cholesterol lowering. Streptozotocin was administered to Yorkshire pigs to induce DM. One month after induction, diabetic pigs were treated with atorvastatin (statin, n = 10), ezetimibe (n = 10) or untreated (n = 10) and evaluated for number of bone marrow and circulating EPCs and femoral artery endothelial function. There was no effect of either medication on cholesterol level. One month after induction of DM prior to administration of drugs, the number of bone marrow and circulating EPCs significantly decreased (P < 0.0001) compared to baseline. Three months after DM induction, the mean proportion of circulating EPCs significantly increased in the atorvastatin group, but not in the control or ezetimibe groups. The control group showed progressive reduction in percentage of flow mediated vasodilatation (no dilatation at 3 months) whereas the atorvastatin group and ezetimibe exhibited vasodilatation, 6% and 4% respectively. DM results in significant impairment of bone marrow and circulating EPCs as well as endothelial function. The effect is ameliorated, in part, by atorvastatin independent of its cholesterol lowering effect. These data suggest a model wherein accelerated atherosclerosis seen with DM may, in part, result from reduction in EPCs which may be ameliorated by treatment with a statin.

Original languageEnglish
Pages (from-to)75-82
Number of pages8
JournalCytometry Part A
Volume75
Issue number1
DOIs
StatePublished - Jan 2009

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Swine
Bone Marrow
Cholesterol
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Vasodilation
Endothelial Cells
Atorvastatin Calcium
Endothelial Progenitor Cells
Femoral Artery
Streptozocin
Dilatation
Atherosclerosis
Control Groups
Pharmaceutical Preparations
Ezetimibe

Keywords

  • Cytometry
  • Diabetes mellitus
  • Endothelial progenitor cells
  • Endothelium
  • Inflammation
  • Statin

ASJC Scopus subject areas

  • Cell Biology
  • Histology
  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Diabetes reduces bone marrow and circulating porcine endothelial progenitor cells, an effect ameliorated by atorvastatin and independent of cholesterol. / Mohler, Emile R.; Shi, Yuquan; Moore, Jonni; Bantly, Andrew; Hamamdzic, Damir; Yoder, Mervin; Rader, Daniel J.; Putt, Mary; Zhang, Lifeng; Parmacek, Michael; Wilensky, Robert L.

In: Cytometry Part A, Vol. 75, No. 1, 01.2009, p. 75-82.

Research output: Contribution to journalArticle

Mohler, ER, Shi, Y, Moore, J, Bantly, A, Hamamdzic, D, Yoder, M, Rader, DJ, Putt, M, Zhang, L, Parmacek, M & Wilensky, RL 2009, 'Diabetes reduces bone marrow and circulating porcine endothelial progenitor cells, an effect ameliorated by atorvastatin and independent of cholesterol', Cytometry Part A, vol. 75, no. 1, pp. 75-82. https://doi.org/10.1002/cyto.a.20691
Mohler, Emile R. ; Shi, Yuquan ; Moore, Jonni ; Bantly, Andrew ; Hamamdzic, Damir ; Yoder, Mervin ; Rader, Daniel J. ; Putt, Mary ; Zhang, Lifeng ; Parmacek, Michael ; Wilensky, Robert L. / Diabetes reduces bone marrow and circulating porcine endothelial progenitor cells, an effect ameliorated by atorvastatin and independent of cholesterol. In: Cytometry Part A. 2009 ; Vol. 75, No. 1. pp. 75-82.
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